Hypercholesterolemia is known to be one of the prime risk factors of cardiovascular disease, such as arteriosclerosis. To date there is still no effective antihypercholesterolemic agent commercially available that has found wide patient acceptance. The bile acid sequestrants seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time and they are not very palatable.
There are agents known, however, that are very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase. These agents include the natural fermentation products compactin and mevinolin and a variety of semi-synthetic and totally synthetic analogs thereof.
The naturally occurring compounds and their semi-synthetic analogs have the following general structural formulae: ##STR2## wherein: R.sup.3 is hydrogen, C.sub.1-5 alkyl or C.sub.1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino;
R.sup.4 is: ##STR3## wherein Q is ##STR4## R.sup.5 is H or OH: R.sup.6 is hydrogen or methyl; and
a, b, c, and d represent optional double bonds, especially where b and d represent double bonds or a, b, c, and d are all single bonds.
U.S. Pat. Nos. 4,231,938, 4,294,926 and 4,319,039 disclose the naturally occurring HMG-CoA reductase inhibitor mevinolin, and the processes for the cultivation of microorganisms of the genus Aspergillis to produce mevinolin as well as the methods utilized to isolate mevinolin from the fermentation broth.
U.S. Pat. No. 4,517,373 discloses semi-synthetic hydroxy containing compounds represented by the above general formula wherein R.sup.4 is ##STR5##
U.S. Pat. No. 4,346,227 and U.S. Pat. No. 4,448,979 also disclose semi-synthetic hydroxy-containing compounds represented by the above general formula wherein R.sup.4 is ##STR6##
U.S. Pat. No. 4,376,863 discloses a fermentation product isolated after cultivation of a microorganism belonging to the genus Aspergillus which has a hydroxy containing butyryloxy side chain and is represented by the above general formula wherein R.sup.4 is ##STR7##
Japanese unexamined patent application No. J59-122,483-A discloses a semi-synthetic hydroxy-containing compound represented by the above general formula wherein R.sup.4 is ##STR8##